Currently, the most effective method for treatment of severe or nonhealing osseous defects is autogenic bone grafting, which involves the transplantation of bone from another part of a patient's body into the defect. Significatn disadvantages are associated with autogenic bone grafting, including donor site morbidity and limited tissue availability. Bone banks have been established to provide an alternative source of bone grafting material, consisting of allogenic freeze-dried bone. Allogenic bone grafts, however, are very expensive and do not heal as well as do fresh autogenic bone grafts.
Attempts to overcome these problems have involved the use of calcium phosphates and apatites. They have been evaluated as either dense or porous implants, with various types and sizes of porosity, including replicas of marine coral. Hydroxylapatite implants are generally considered to be somewhat more stable in vivo than tricalcium phosphate implants, which show a greater tendency to be absorbed. These ceramic materials are generally implanted in particulate form to fill bone defects, which can present handling difficulties.
Hydroxylapatite and tricalcium phosphate particles both apparently provide a useful scaffold for bone ingrowth into a bone defect, but these ceramics do not have any inductive or accelerating effect on bone repair. A significant problem with implants of calcium phosphate mineral particles relates to keeping the particles at the implantation site. Various approaches have been used to try to inhibit migration of the mineral particles from the implanation site, including adding the particles to a collagen matrix and mixing the particles with plaster of paris (See European patent application No. 197,693, and U.S. Pat. No. 4,619,655, respectively).
Demineralized, lyophilized bone has also been used as a component of osteoinductive agents. See M. R. Urist, Science, 150, 893 (1965). Recently, M. R. Urist et al., in U.S. Pat. No. 4,294,753 and in Proc. Natl. Acad. Sci. U.S.A., 76, 1828 (1979), have disclosed the use of particles such as "protein osteoinductive factor" (OF) derived from such bone matrices with various carriers to induce new bone formation. However, it can be difficult to reproducibly prepare these materials, which must be characterized by various bioassay systems. See, for example, R. Nathan et al., U.S. Pat. No. 4,563,350.
Sauk and Van Kampen disclose compositions which are effective to promote new bone formation upon introduction of the composition into osseous defects in U.S. Pat. application Ser. No. 811,677, filed Dec. 20, 1985, now U.S. Pat. No. 4,698,326, the disclosure of which is incorporated by reference herein. Preferred compositions are prepared by mixing a phosphophoryn calcium salt and type I collagen in a ratio of the salt to the collagen of about 3.0-0.1:1 to yield a solid composition. These compositions have the appearance and texture of soft sponges. The low mechanical strength and highly compressible nature of these sponges can limit their application in the treatment of segmental defects.
Therefore, a need exists for physically stable compositions useful to repair osseous defects which can be readily manipulated during formulation and implantation. A further need exists for compositions useful for osseous repair which can be prepared reproducibly, e.g., which incorporate well characterized components.